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Molecular basis of HNPCC: Mutations of MMR genes
Author(s) -
Papadopoulos Nickolas,
Lindblom Annika
Publication year - 1997
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1997)10:2<89::aid-humu1>3.0.co;2-h
Subject(s) - biology , genetics , dna mismatch repair , germline mutation , gene , germline , mutation , lynch syndrome , dna repair
Hereditary nonpolyposis colorectal cancer (HNPCC) is inherited as a dominant disorder caused by germline defects in one of at least four mismatch repair (MMR) genes. Two of these genes, hMSH2 and hMLH1 , account for the vast majority of the germline mutations in HNPCC kindreds, whereas hPMS1 and hPMS2 are mutated in only few families. MMR genes also are susceptible to somatic mutations in sporadic tumors. The mutational spectrum of the MMR genes shows no predominant type of mutation. Furthermore, the mutations are spread throughout the length of the genes, with no significant hot spots. Identification of MMR genes as the cause of HNPCC made presymptomatic diagnosis a reality. However, the presence of multiple genes and the heterogeneity of mutations present challenges to the development of diagnostic tests for this disease. Hum Mutat 10:89–99, 1997. © 1997 Wiley‐Liss, Inc.